Author

Bakota, Erica Laraine

Date

2011

Advisor

Hartgerink, Jeffrey D.

Degree

Doctor of Philosophy

Abstract

Peptides are materials that, as a result of their polymeric nature, possess enormous
versatility and customizability. Multidomain peptides are a class of peptides that selfassemble
to form stable, cytocompatible hydro gels. They have an ABA block motif, in
which the A block is composed of charged amino acids, such as lysine, and the B block
consists of alternating hydrophilic and hydrophobic amino acids, such as glutamine and
leucine. The B block forms a facial amphiphile that drives self-assembly. The charged A
blocks simultaneously limit self-assembly and improve solubility. Self-assembly is
triggered by charge screening of these charged amino acids, enabling the formation of ~sheet
fibers. The development of an extended nanofiber network can result in the
formation of a hydrogel.
Systematic modifications to both the A and B blocks were investigated, and it was
found that sequence modifications have a large impact on peptide nanostructure and
hydrogel rheology. The first modification examined is the substitution of amino acids
within the hydrophilic positions of the B block. The second set of modifications
investigated was the incorporation of aromatic amino acids in the B block. Finally, the
charged block was varied to generate different net charges on the peptides, a change
which impacted the ability to use these peptides in cell culture.
Two applications of multi domain peptide nanofibers are explored, the first of
which is the delivery of novel therapies in vivo. One multidomain peptide is able to form
hydrogels that undergo shear-thinning and rapid recovery. This gel can be loaded with
cytokines and growth factors that have been secreted by embryonic stem cells, and these
molecules can be subsequently released in a therapeutic setting. Another application for
multidomain peptide is their use as biocompatible surfactants. Single-walled carbon
nanotubes have been widely investigated for their unique optical and electrical properties,
but their solubility in aqueous systems has been a challenge. Multidomain peptides
solubilize carbon nanotubes, are less cytotoxic than detergents such as SDBS, and
preserve the ability of carbon nanotubes to fluoresce. Some of these peptides are also
compatible with cell culture, allowing the delivery of single-walled carbon nanotubes to
cells.